A large, long-term study of more than 52,000 women in Israel has found that initiation of contemporary hormone replacement therapy (HRT) among women ages 45 to 59 was not associated with an increased risk of heart attack, stroke, blood clots or death. The independent, preliminary research, which had an average follow-up of 12 years, will be presented at the American Heart Association’s Scientific Sessions 2026, a premier global exchange of cardiovascular science, taking place Nov. 6-9 in Chicago.
The findings could have significant implications for how women and their healthcare providers approach menopause management. Concerns about cardiovascular safety have been a major reason many women decline hormone therapy, and why some clinicians hesitate to prescribe it. “Concerns that hormone replacement therapy may affect the heart is one of the most common reasons women decline hormone therapy to manage menopause symptoms, and why some healthcare professionals may hesitate to offer it,” said lead study researcher Ronen Arbel, Ph.D., a researcher in the community medical services division of Clalit Health Services in Tel Aviv, Israel, and with Sapir College’s Maximizing Health Outcomes Research Lab in Sderot, Israel.
Previous randomized trials had linked HRT to cardiovascular harm, but those results were mixed and largely based on older formulations, higher doses, and women who started therapy long after menopause. Current guidelines from the American College of Obstetricians and Gynecologists recommend starting HRT within 10 years of menopause onset and before age 60. In November 2025, the FDA removed the “black box” warnings from HRT products after a comprehensive review found that HRT is not associated with increased risk of cardiovascular disease, breast cancer or dementia.
The new study evaluated data from Clalit Health Services for 52,330 women aged 45-59 with no history of heart disease, blood clots or cancer. Half had started HRT, primarily oral or transdermal (patch) or gel, while the other half had recently seen a gynecologist but did not begin HRT. Researchers matched the groups by age, BMI, cardiometabolic risk factors, smoking status and socioeconomic status, and followed them for up to 23 years. After an average of 12 years, health outcomes were similar: 4.4% of the HRT group experienced a heart attack, stroke or related heart disease versus 4.6% of the no-HRT group; death before age 80 occurred in 1.3% versus 1.2%; and blood clots occurred in 0.33% of both groups. Results were consistent across all HRT formulations and administration routes.
“Our results indicate that, for women in their mid-forties to late fifties with no history of heart disease or blood clots, the currently available hormone therapies prescribed to manage menopause symptoms do not appear to raise the risk of heart attack, stroke, clots or early death, even after long-term use,” Arbel said. Stacey E. Rosen, M.D., FAHA, past volunteer president of the American Heart Association (2025-2026) and executive director of the Katz Institute for Women’s Health at Northwell Health, who was not involved in the study, said the findings “add to growing evidence that today's hormone therapy options may not increase the risk of heart disease, stroke or blood clots for healthy women who begin treatment around the time of menopause.”
The study is observational and cannot prove a direct connection. Researchers also noted potential differences among women not captured in health records, such as exercise, diet and menopause symptom severity. The findings are considered preliminary until published in a peer-reviewed journal. The research adds to ongoing efforts to clarify cardiovascular risk during the menopause transition, as discussed in the American Heart Association’s scientific statement on Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention. For women and clinicians weighing menopause treatment, the results may help inform more balanced conversations about benefits and risks. The full abstract and the Online Program Planner are available for further details. Additional resources include the release link and a Spanish news release. General information on atherosclerotic cardiovascular disease and venous thromboembolism is also available.
